Biology subjects

Jaubert, J.

Publications and source records attributed to Jaubert, J..

4 recordsLinked to original sources

bioRxiv2025

An atypical F-type ATPase is necessary for the function of the antibody cleavage system MIB-MIP in mycoplasmas.

Mycoplasmas are genome-reduced, parasitic bacteria colonizing a broad range of organisms, including most livestock species and humans. They are often pathogenic, and have evolved an arsenal of mechanisms to counter their hosts immune response. Among these, the Mycoplasma Immunoglobulin Binding/Protease (MIB-MIP) system appears to be particularly important, and is conserved in the majority of mycoplasma species. Through genomics analysis, we show that MIB-MIP systematically co-occurs with a cluster of 7 coding sequences corresponding to an atypical Type 3 F-ATPase termed "F1-like X0". Working in the model organism Mycoplasma mycoides subsp. capri, we first performed a proteomics analysis to confirm that this ATPase is indeed expressed. We then generated two mutant strains in which the putative ATPase was either fully deleted, or rendered catalytically inactive through replacement of a conserved lysine residue in the Walker A motif of the ATPase {beta}-like subunit. Functional assays in presence of immune serum showed that both mutants are unable to protect themselves from agglutination by immunoglobulins despite the MIB-MIP system still being present. We then attempted to affinity-purify the atypical F1-like X0 ATPase from the membrane of its native host. Although the complex appears to be labile, under cross-linking conditions we were able to co-purify all its predicted components, as well as both MIB and MIP. These results allow us to attribute a function to Type 3 F-ATPase, namely to participate in the evasion from the humoral immune response in mycoplasmas, in conjunction with the MIB-MIP system through a currently unknown mechanism.

microbiology↗

bioRxiv2021

A mouse-adapted SARS-CoV-2 strain replicating in standard laboratory mice.

SARS-CoV-2 has infected almost 200 million humans and caused over 4 million deaths worldwide. Evaluating countermeasures and improving our understanding of COVID-19 pathophysiology require access to animal models that replicate the hallmarks of human disease. Mouse infection with SARS-CoV-2 is limited by poor affinity between the virus spike protein and its cellular receptor ACE2. We have developed by serial passages the MACo3 virus strain which efficiently replicates in the lungs of standard mouse strains and induces age-dependent lung lesions. Compared to other mouse-adapted strains and severe mouse models, infection with MACo3 results in mild to moderate disease and will be useful to investigate the role of host genetics and other factors modulating COVID-19 severity.

microbiology↗

bioRxiv2021

The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice

Receptor recognition is a major determinant of viral host range, infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with novel hosts, and the high mutation rate of RNA viruses may explain their frequent host shifts. SARS-CoV-2 extensive circulation in humans results in the emergence of variants, including variants of concern (VOCs) with diverse mutations notably in the spike, and increased transmissibility or immune escape. Here we show that, unlike the initial and Delta variants, the three VOCs bearing the N501Y mutation can infect common laboratory mice. Contact transmission occurred from infected to naive mice through two passages. This host range expansion likely results from an increased binding of the spike to the mouse ACE2. Together with the observed contact transmission, it raises the possibility of wild rodent secondary reservoirs enabling the emergence of new variants.

microbiology↗

bioRxiv2019

A loss-of-function mutation in Itgal contributes to the high susceptibility of Collaborative Cross strain CC042 to Salmonella infections

Salmonella are intracellular bacteria that are found in the gastrointestinal tract of mammalian, avian, and reptilian hosts. They are one of the leading causes of foodborne infections and a major threat for human populations worldwide. Mouse models have been extensively used to model distinct aspects of the human Salmonella infections in vivo and have led to the identification of several host susceptibility genes. We have investigated the susceptibility of Collaborative Cross strains to intravenous infection with Salmonella Typhimurium as a model of human systemic invasive infection. In this model, strain CC042 displayed extreme susceptibility with very high bacterial loads and mortality. CC042 mice showed lower spleen weight and decreased splenocyte numbers before and after infection, affecting mostly CD8+ T cells, B cells, and all myeloid populations. Uninfected mice also had lower thymus weight with reduced total number of thymocytes and double negative and (CD4+, CD8+) double positive thymocytes. Analysis of bone marrow resident hematopoietic progenitors showed a strong bias against lymphoid primed multipotent progenitors, which are the precursors of T, B and NK cells. An F2 cross between CC042 and C57BL/6N identified two significant QTLs on chromosome 7 (Stsl6 and Stsl7) with WSB-derived susceptible alleles. A private variant in the integrin alpha L (Itgal) gene is carried by CC042 in the Stsl7 QTL region. A quantitative complementation test confirmed the impact of Itgal loss of function in a (C57BL/6JxCC042)F1 background, but not in a C57BL/6J inbred background. These results further emphasize the utility of the Collaborative Cross to identify new host genetic variants controlling susceptibility to infections and improve our understanding of the function of the Itgal gene.\n\nAuthor summarySalmonella are one of the leading causes of foodborne infections and a major threat for human populations worldwide. Not all humans are equally susceptible to Salmonella infection. Some individuals will develop minor symptoms and recover while others develop severe illness and might die. Mouse models are used to study distinct aspects of human Salmonella infection in vivo. We used a new genetically diverse mouse population to investigate host susceptibility differences to Salmonella infection. We identified one mouse strain with an extreme susceptibility to infection characterized by very high bacterial loads and mortality. Mice of this strain had small thymus and spleen, two organs which are very important for producing a fully mature immune system. We showed that the strains immune response is impaired and that its extreme susceptibility to Salmonella infection is due to multiple genes defects. We identified a loss-of-function mutation in the Itgal gene (Integrin Subunit Alpha L) that plays a central role in the immune response to infection. This gene explains part of the susceptibility and other gene(s) involved remain to be identified. Our results emphasize how new genetically diverse animal models can lead to the identification of new host genetic variants controlling susceptibility to pathogens and improve our understanding of human infections.

immunology↗